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The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis.

Jiménez-Medina E, Berruguilla E, Romero I, Algarra I, Collado A, Garrido F, Garcia-Lora A - BMC Cancer (2008)

Bottom Line: The inhibition ranged from 22 to 84%.Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression.In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Servicio de Análisis Clínicos e Inmunologia, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Av, de las Fuerzas Armadas 2, 18014 Granada, Spain. evajimenez@fundacionhvn.org

ABSTRACT

Background: Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated.

Methods: The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells.

Results: PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation.

Conclusion: These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.

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Related in: MedlinePlus

In vitro activity of neuraminidase treated-PSK. a) A549 tumour cell line was cultured with neuraminidase-treated PSK or PSK. A549 tumour cells (20 × 104) were seeded in culture flask and treated with PSK for 96 h, estimating cell viability by means of Trypan blue exclusion. Both agents produced a similar inhibition ofproliferation. b) NKL cell line was cultured with PSK or neuraminidase treated-PSK and proliferation was determined by BrdU incorporation and absorbance measurement. Both agents induced a similar increase of proliferation. Each column represents the mean of five independent experiments ± SD. *P < 0.001 versus control.
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Figure 3: In vitro activity of neuraminidase treated-PSK. a) A549 tumour cell line was cultured with neuraminidase-treated PSK or PSK. A549 tumour cells (20 × 104) were seeded in culture flask and treated with PSK for 96 h, estimating cell viability by means of Trypan blue exclusion. Both agents produced a similar inhibition ofproliferation. b) NKL cell line was cultured with PSK or neuraminidase treated-PSK and proliferation was determined by BrdU incorporation and absorbance measurement. Both agents induced a similar increase of proliferation. Each column represents the mean of five independent experiments ± SD. *P < 0.001 versus control.

Mentions: Tumour cell proliferation inhibition was compared among different PSK variants. Neuraminidase treatment digests glicosylated proteins. A549 tumour cell line was cultured in medium alone (control) or with PSK (100 μg/ml) or neuraminidase-treated PSK (100 μg/ml) for 4–6 days and then counted using trypan blue. No significant differences in proliferation inhibition were found between PSK and neuraminidase-treated PSK (Fig. 3a). The same results were found for sugar-rich and protein-rich PSK variants as for PSK (data not shown).


The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis.

Jiménez-Medina E, Berruguilla E, Romero I, Algarra I, Collado A, Garrido F, Garcia-Lora A - BMC Cancer (2008)

In vitro activity of neuraminidase treated-PSK. a) A549 tumour cell line was cultured with neuraminidase-treated PSK or PSK. A549 tumour cells (20 × 104) were seeded in culture flask and treated with PSK for 96 h, estimating cell viability by means of Trypan blue exclusion. Both agents produced a similar inhibition ofproliferation. b) NKL cell line was cultured with PSK or neuraminidase treated-PSK and proliferation was determined by BrdU incorporation and absorbance measurement. Both agents induced a similar increase of proliferation. Each column represents the mean of five independent experiments ± SD. *P < 0.001 versus control.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2291471&req=5

Figure 3: In vitro activity of neuraminidase treated-PSK. a) A549 tumour cell line was cultured with neuraminidase-treated PSK or PSK. A549 tumour cells (20 × 104) were seeded in culture flask and treated with PSK for 96 h, estimating cell viability by means of Trypan blue exclusion. Both agents produced a similar inhibition ofproliferation. b) NKL cell line was cultured with PSK or neuraminidase treated-PSK and proliferation was determined by BrdU incorporation and absorbance measurement. Both agents induced a similar increase of proliferation. Each column represents the mean of five independent experiments ± SD. *P < 0.001 versus control.
Mentions: Tumour cell proliferation inhibition was compared among different PSK variants. Neuraminidase treatment digests glicosylated proteins. A549 tumour cell line was cultured in medium alone (control) or with PSK (100 μg/ml) or neuraminidase-treated PSK (100 μg/ml) for 4–6 days and then counted using trypan blue. No significant differences in proliferation inhibition were found between PSK and neuraminidase-treated PSK (Fig. 3a). The same results were found for sugar-rich and protein-rich PSK variants as for PSK (data not shown).

Bottom Line: The inhibition ranged from 22 to 84%.Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression.In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Servicio de Análisis Clínicos e Inmunologia, Hospital Universitario Virgen de las Nieves, Universidad de Granada, Av, de las Fuerzas Armadas 2, 18014 Granada, Spain. evajimenez@fundacionhvn.org

ABSTRACT

Background: Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated.

Methods: The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells.

Results: PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation.

Conclusion: These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.

Show MeSH
Related in: MedlinePlus